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PREVENTION OF SECONDARY DAMAGE
Severe TBI, accompanied by persistent loss of consciousness, is associated with swelling of the brain (cerebral edema) and increased intra-cranial pressure. Unchecked swelling expands the brain tissue until it pushes against the skullcase, resulting in crushing force exerted on arteries which squeeze shut. This can cause death or irreversible brain damage from anoxia, the failure of oxygenated blood to reach brain tissue. In contemporary practice, an unconscious patient who sustained significant head trauma, will get a CT scan. If the scan is positive for cerebral edema (or if the scan is negative but the patient is over 40 years old and his systolic blood pressure is under 90 mm Hg.) the neurosurgeon will order intra-cranial pressure monitoring. If the ICP hit the 20-25 mm Hg. area, the neurosurgeon will order boluses of Mannitol to reverse the brain swelling, which will bring down the ICP to safe levels. In earlier days neurosurgeons used a combination of diuretcs and cortico-steroids to reverse brain swelling, but this has been phased out due principally to the harmful side effects of steroids. For the 10-15% of patients whose brains remain dangerously swollen even after administration of Mannitol, neurosurgeons use high dose barbiturates to lower cerebral metabolism which in turn lowers cerebral blood flow and cerebral blood volume.

Brain trauma can initiate over-excitation of neurons with onset of early seizures or creation of permanent seizure foci in some patients, especially those with depressed skull fracture, cortical contusion or intra-cranial bleeding in the form of an epidural hematoma, subdural hematoma or intracerebral hematoma. Physicians want to avoid early seizures because they raise blood pressure, lower oxygen delivery or release a toxic excess of neurotransmitters. They also want to prevent delayed onset of a chronic seizure disorder. However, administration of anti-convulsants in the hospital carries certain risks. Thus doctors will use them preventively only in patients viewed at high risk of having a seizure, and they will discontinue the anti-convulsants at the earliest possible time. Use of Dilantin in such patients has a high rate of success in preventing seizures from occurring after they leave the hospital. The old practice of giving prophylatic Dilantin to every patient who sustained a head injury has been phased out.

Another complication of severe TBI is the excito-toxic response, in which hugely excessive quantities of glutamate (an excitatory neurotransmitter which plays a role in stroke and seizure) are released into the brain. In studies on rats, researchers have been relatively successful in finding neuro-protective drugs, which spare the rat brains from excito-toxic damage. So far experimental administration of the same agents on humans has not worked. Research continues.

A new agent called Dexanabinol made by the Pharmos Corporation appears to reduce intra-cranial pressure, suppress inflammation and protect brain cells from excito-toxic damage by blocking massive influx of calcium ions across cell membranes. As of Spring 2001 Dexanabinol had passed the FDA's phase I and II clinical trials. Phase III trials for safety and efficacy are beginning this summer. Dr. Lawrence Marshall at UC San Diego Medical Center says Exanabinol holds real promise for being the first ever drug approved by the FDA to reduce damage following a severe TBI.